Retroviral vectors have been constructed that express one or more of the following gene products: sCD4 (or it's derivatives), alpha-interferon, transdominant rev mutants, and an HIV inducible diphtheria toxin. The goal of this work is to engineer human lymphocytes such that they manifest anti-HIV activity and thus may prevent HIV infection or decrease viral replication. Initial work has concentrated on construct retroviral vectors that produce a secreted form of the helper/inducer T-cell antigen, CD4 (sCD4). It has been demonstrated by cocultivation that transduced cells (producing sCD4) can protect HIV susceptible cell from infection by HIV. Further , it was shown that sCD4 transduced primary human lymphocytes can be directly protected from HIV infection. All of these anti-HIV systems are currently being tested in AIDS animal models, specifically, Hu-PBL-SCID mice.